Despite the central importance of synaptic transmission in nervous system function, the properties of variable synaptic efficacy are poorly understood. The goal of the proposed research is to (a) clearly define the relationship between repetitive stimulation and facilitation, tetanic potentiation, post-tetanic potentiation, and depression of transmitter release by means of a quantitative description of this relationship, and (b) explore this relationship within the framework of the quantal and calcium hypotheses of transmitter release. Depending on the experiment, estimates of the amount of transmitter released at the vertebrate neuromuscular junction will be made from measurements of end- plate potentials recorded intracellularly or extracellularly or from measurements of end-plate currents recorded under under voltage clamp. A variety of frequencies and patterns of repetitive stimulation and pharmacological agents will be used to probe the nerve terminal. Models for the mechanism of transmitter release will be formulated and evaluated by comparing experimental data to theoretical data obtained by simulation of the models on a digital computer.